Caspase-1 activity is required to bypass macrophage apoptosis upon Salmonella infection.
ABSTRACT Here we report AWP28, an activity-based probe that can be used to biochemically monitor caspase-1 activation in response to proinflammatory stimuli. Using AWP28, we show that apoptosis is triggered upon Salmonella enterica var. Typhimurium infection in primary mouse bone marrow macrophages lacking caspase-1. Furthermore, we report that upon Salmonella infection, inflammasome-mediated caspase-1 activity is required to bypass apoptosis in favor of proinflammatory pyroptotic cell death.
Article: Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells.Infection and Immunity 05/2005; 73(4):1907-16. · 4.16 Impact Factor
Article: All that glitters is not gold: all that FLICA binds is not caspase. A caution in data interpretation--and new opportunities.Cytometry Part A 09/2007; 71(8):536-7. · 3.73 Impact Factor
Article: Salmonella-Induced Caspase-2 Activation in Macrophages: A Novel Mechanism in Pathogen-Mediated Apoptosis[show abstract] [hide abstract]
ABSTRACT: The enterobacterial pathogen Salmonella induces phagocyte apoptosis in vitro and in vivo. These bacteria use a specialized type III secretion system to export a virulence factor, SipB, which directly activates the host's apoptotic machinery by targeting caspase-1. Caspase-1 is not involved in most apoptotic processes but plays a major role in cytokine maturation. We show that caspase-1–deficient macrophages undergo apoptosis within 4–6 h of infection with invasive bacteria. This process requires SipB, implying that this protein can initiate the apoptotic machinery by regulating components distinct from caspase-1. Invasive Salmonella typhimurium targets caspase-2 simultaneously with, but independently of, caspase-1. Besides caspase-2, the caspase-1–independent pathway involves the activation of caspase-3, -6, and -8 and the release of cytochrome c from mitochondria, none of which occurs during caspase-1–dependent apoptosis. By using caspase-2 knockout macrophages and chemical inhibition, we establish a role for caspase-2 in both caspase-1–dependent and –independent apoptosis. Particularly, activation of caspase-1 during fast Salmonella-induced apoptosis partially relies on caspase-2. The ability of Salmonella to induce caspase-1–independent macrophage apoptosis may play a role in situations in which activation of this protease is either prevented or uncoupled from the induction of apoptosis.Journal of Experimental Medicine 11/2000; · 13.85 Impact Factor